Comparative Analysis of IDegLira versus Insulin Glargine in Short-Term Intensive Therapy for Overweight or Obese Patients with Type 2 Diabetes Mellitus

Comparative Analysis of IDegLira versus Insulin Glargine in Short-Term Intensive Therapy for Overweight or Obese Patients with Type 2 Diabetes Mellitus | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparative Analysis of IDegLira versus Insulin Glargine in Short-Term Intensive Therapy for Overweight or Obese Patients with Type 2 Diabetes Mellitus yaping sun, Xiaolei Li, Liwu Xu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8921856/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 7 You are reading this latest preprint version Abstract Purpose To compare the efficacy of insulin degludec/liraglutide (IDegLira) versus insulin glargine, both combined with insulin aspart, for short-term intensive glycemic control in overweight or obese patients with type 2 diabetes mellitus (T2DM). Method Severely hyperglycemic overweight/obese T2DM patients were randomly assigned to receive either IDegLira plus insulin aspart (observation group) or insulin glargine plus insulin aspart (control group). Continuous glucose monitoring systems (CGMS) were used to assess glycemic control, insulin requirements, pancreaticβ-cell function, and insulin resistance over a seven-day intensive therapy period. Result The observation group exhibited a higher time in range (TIR) compared with the control group ( P = 0.007). Measures of glycemic variability, including time above range (TAR), mean of daily differences (MODD), mean glucose (MG), standard deviation (SD), and coefficient of variation (CV), were all significantly lower in the IDegLira group ( P < 0.01). After seven days of treatment, the reduction in C-peptide-based homeostasis model assessment of insulin resistance (HOMA-IR-CP) was greater in the IDegLira group ( P = 0.001), while the improvement in C-peptide-based homeostasis model assessment of β-cell function (HOMA islet-CPDM) was markedly greater( P < 0.001). The IDegLira group also required a lower total daily insulin dose at the end of treatment, achieved glycemic targets more rapidly, and demonstrated a higher rate of excellent glycemic control ( P = 0.001). Conclusion IDegLira combined with insulin aspart provides superior short-term intensive glycemic control compared with insulin glargine plus insulin aspart in overweight or obese patients with T2DM, with faster target achievement, improved glycemic stability, reduced insulin requirements, and greater improvements in insulin resistance and β-cell function. Overweight/obesity Type 2 diabetes IDegLira Insulin glargine Short-term intensive glucose control Figures Figure 1 Figure 2 Introduction The latest data from the International Diabetes Federation (IDF) indicate that 537 million adults worldwide currently have diabetes, and this number is projected to increase to 643 million by 2030. 1 Overweight and obesity are prominent features among individuals with T2DM globally, affecting approximately 85% of patients. 2 Studies have shown that visceral fat accumulation is associated with insulin resistance and represents one of the major risk factors for the development of this disease. 3 , 4 Overweight and obesity increase the difficulty of blood glucose control in diabetic patients and elevate the risk of cardiovascular disease, while early intensive glycemic control can reduce the metabolic memory effect of vascular complications. 5 In overweight or obese patients with T2DM, treatment strategies should address not only glycemic control but also weight reduction and the improvement of insulin resistance. Short-term intensive insulin therapy is an effective approach for patients with T2DM presenting with severe hyperglycemia. 6 The current standard intensive insulin therapy typically involves either continuous subcutaneous insulin infusion with short-or rapid-acting insulin or a regimen of preprandial short-or rapid-acting insulin combined with insulin glargine; however, this approach is often less effective in overweight or obese patients with T2DM who exhibit marked insulin resistance. 7 , 8 The 2022 American Diabetes Association (ADA) Standards of Care state that for patients with T2DM inadequately controlled on basal insulin and oral antihyperglycemic agents, a basal insulin–GLP-1 receptor agonist (GLP-1 RA) injection may be considered as a treatment option. 9 In 2016, the U.S.Food and Drug Administration (FDA) approved the basal insulin GLP-1 receptor agonist injection—IDegLira—for the treatment of diabetes. 10 This study aimed to evaluate the short-term intensive effects of IDegLira versus insulin glargine, each combined with insulin aspart, in overweight or obese patients with T2DM, with the goal of exploring novel strategies for short-term insulin-based glycemic management in this population. Materials and Methods Research subjects A total of 126 eligible overweight or obese patients with T2DM hospitalized in the Endocrinology Department between October 2024 and June 2025 were randomly assigned in a 1:1 ratio to the control group (n = 63) or observation group (n = 63). Inclusion, exclusion, and grouping criteria Inclusion Criteria: (1) Met the diagnostic and classification criteria for T2DM; (2) Had glycated hemoglobin (HbA1c) ≥ 9.0% or fasting plasma glucose (FPG) ≥ 11.1 mmol/L; (3) Had a body mass index (BMI) ≥ 24 kg/m² or a waist circumference > 90 cm in males and > 85 cm in females; (4) Were aged between 18 and 80 years; (5) The patient and family members were informed about the study and had signed the consent form. Exclusion Criteria: (1) Had severe infection or acute complications of diabetes; (2) Had severe heart, liver, or kidney failure; (3) Were pregnant, breastfeeding, or trying to conceive; (4) Were allergic to the drugs used in this study; (5) Had sarcopenia, medullary thyroid carcinoma (including a personal or family history), or multiple endocrine neoplasia type 2. (6) Patients with severe non-proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) were excluded. Treatment Methods Eligible patients were randomly assigned to the control or observation group in a 1:1 ratio using a random number table, and intensive therapy was administered for 1 week. Patients in the observation group received preprandial subcutaneous injections of insulin aspart (Novo Nordisk, 3 mL:300 U) combined with once-daily subcutaneous injections of IDegLira (Novo Nordisk, 3 mL containing 300 U insulin degludec and 10.8 mg liraglutide). Patients in the control group received preprandial subcutaneous injections of insulin aspart combined with once-daily subcutaneous injections of insulin glargine (Sanofi-Aventis Deutschland GmbH, 1.5 mL:450 U per prefilled pen, 300U/ml). The initial total insulin dose in both the observation and control groups was 0.5 U/(kg·d). The starting dose of insulin glargine or IDegLira constituted 50% of the total dose, with the remaining 50% distributed equally among the three pre-meal doses of insulin aspart at a ratio of 1:1:1. The starting dose of IDegLira did not exceed 16 units in principle, with a maximum dose not exceeding 50 units. Dosage was adjusted based on fasting blood glucose (FBG) levels: when FBG was > 7.8 mmol/L, the dose was increased by 4 U; when 6.1 mmol/L ≤ FBG ≤ 7.8 mmol/L, the dose was increased by 2 U; when 4.4 mmol/L ≤ FBG < 6.1 mmol/L, no adjustment was made; when FBG was < 4.4 mmol/L, the dose was reduced by 2 U. The method for adjusting the initial dose of insulin glargine in the control group was the same as described above. Pre-meal insulin doses were adjusted as needed based on pre-meal blood glucose levels before the next meal, with dose adjustments performed every 2–3 days. All participants in both groups received the same standardized lifestyle management and education program, including dietary and exercise counseling. Both groups were equipped with the same continuous glucose monitoring system (manufacturer: Shenzhen Silicon-based Sensor Technology Co., Ltd.; model: GS1-10). Data Collection On the first day of hospitalization, clinical and laboratory data were collected, including age, sex, height, weight, BMI, duration of type 2 diabetes, FPG, glycated hemoglobin (HbA1c), fasting C-peptide (FCP), and adiponectin (APN). On day 7 of treatment, the achievement of the composite endpoint for high-quality glycemic control was assessed, which required patients to meet all three of the following criteria: (1) efficacy: TIR > 70%; (2) stability: CV < 36%; and (3) safety: no hypoglycemic events (3.0 mmol/L). Hypoglycemia, gastrointestinal symptoms, and other adverse events were recorded, along with total daily insulin dose on the final day(U/kg/day), FCP, and APN levels. C-peptide–based indices of insulin resistance (HOMA-IR-CP) and β-cell function (HOMA islet-CPDM) were calculated before and after treatment using FCP, according to the following formulas: HOMA-IR-CP = 1.5 + FPG×FCP/2800; HOMA islet-CPDM = 0.27×FCP/(FPG − 3.5) 11,12 The CGMS sensor kit was used for a 7-day monitoring period. The glycemic target in the reports was set at 3.9–10.0 mmol/L. Observed indicators included TIR, TAR, time below range (TBR; 3.9 mmol/L or < 2.9 mmol/L), largest amplitude of glucose excursion (LAGE), mean amplitude of glycemic excursions (MAGE), MODD, MG, SD, and CV. Statistical Methods Statistical analysis was performed using SPSS version 26.0 (SPSS Inc., Chicago, IL, USA) and Prism software (GraphPad, version 10.6.0). Continuous variables with a normal distribution were expressed as mean±standard deviation(Mean ± SD) and analyzed using the t-test or analysis of variance(ANOVA). Non-normally distributed data were presented as median with interquartile range and compared using nonparametric tests (Mann-Whitney U). Categorical variables were expressed as frequency (n) and percentage and analyzed using the chi-square test. Paired t-tests were used to compare pre-and post-treatment parameters within groups. Fisher's exact test was applied when appropriate. Two-sided P -values < 0.05 were considered statistically significant. Results Comparison of Baseline Characteristics Between the Two Patient Groups There were no significant differences between the two groups in baseline characteristics, including age, sex, BMI, HbA1c, and duration of type 2 diabetes, as well as metabolic and islet function parameters ( P > 0.05) (Table 1 ). Table 1 Baseline Characteristics of Randomized Participants Clinical Data Control group (n = 63) Observation group (n = 63) P -value Gender (Male: Female) 33: 30 36: 27 0.591 Age(years) 58.48 ± 1.27 55.81 ± 1.34 0.15 Duration of illness (years) 4(3,6) 4(3,5) 0.739 BMI (kg/m2) 28.57(25.95, 30.32) 27.99(25.97, 30.48) 0.610 HbA1c(%) 10.2(8.67,11.42) 10.1(8.9,11.2) 0.639 FPG(mmol/L) 10.6(8.1,13.4) 10.1(8.2,13.7) 0.874 FCP (pmol/L) 440.23(271.42,562.70) 486.57(347.55,662.00) 0.127 APN(mg/L) 7.79(4.4,9.8) 7.0(5.2,11.0) 0.857 HOMA-IR-CP 3.19(2.65,3.89) 3.47(2.75,4.04) 0.273 HOMAislet-CPDM 17.08(10.43,25.64) 21.28(13.11,29.38) 0.134 Note: BMI: Body mass index; FPG: Fasting Plasma Glucose; FCP: Fasting C-peptide; APN: Adiponectin; HOMA-IR-CP: C-peptide Insulin Resistance Index; HOMAislet-CPDM: C-peptide Islet Function Index Comparison of Post-treatment Metabolic and Islet Function Parameters Between the Two Groups After 7 days of treatment, there were no significant differences between the two groups in APN, FCP, or their corresponding change values (Δ)( P > 0.05). In contrast, significant differences were observed between the two groups in FPG, HOMA-islet-CPDM, and their changes (Δ) ( P < 0.05). Post-treatment FPG in the observation group was significantly lower than that in the control group [5.2(5.0-5.5) mmol/L vs.7.5(6.6–8.4) mmol/L, P < 0.001], and the decrease in FPG (ΔFPG) was also markedly greater [4.7(3-8.7) mmol/L vs.2.9(0.4–5.8) mmol/L, P < 0.001]. HOMA-islet-CPDM increased significantly in the observation group[73.28(44.05-100.09)vs.25.08(15.79–38.73), P < 0.001], and its change value (Δ) was also higher than that in the control group ( P < 0.001), indicating a more pronounced improvement in β-cell function. A significantly greater reduction in HOMA-IR-CP was observed in the observation group compared with the control group ( P = 0.005), despite comparable post-treatment levels between groups, indicating a more pronounced improvement in insulin resistance (Table 2 , Fig. 1 ). Table 2 Comparison of Post-treatment Metabolic and Islet Function Parameters Between the Two Groups Clinical Data Control group (n = 63) Observation group (n = 63) P -value FPG (mmol/L) Post-treatment 7.5(6.6,8.4) 5.2(5.0,5.5) <0.001 b --△Change 2.9(0.4,5.8) 4.7(3,8.7) <0.001 APN (mg/L) Post-treatment 7.4(4.7,10.0) 7.3(5.2,10.61) 0.547 --△Change -0.05(-0.6,0.67) -0.1(-0.7,0.6) 0.914 FCP (pmol/L) Post-treatment 364.10(231.70,589.18) 446.85(258.18,628.90) 0.162 --△Change 36.41(-72.82,139.02) 23.17(-86.06,175.43) 1.000 HOMA-IR-CP Post-treatment 2.51(2.08,3.08) 2.36(1.96, 2.75) 0.104 --△Change 0.60(-0.05,1.35) 0.98(0.41,1.60) 0.005 HOMA islet-CPDM Post-treatment 25.08(15.79,38.73) 73.28(44.05,100.09) <0.001 --△Change 7.18(-1.79,16.94) 46.98(27.73,77.72) <0.001 Note: FPG: Fasting Plasma Glucose; FCP: Fasting C-peptide; APN: Adiponectin; HOMA-IR-CP: C-peptide Insulin Resistance Index; HOMAislet-CPDM: C-peptide Islet Function Index Comparison of CGMS Metrics Between the Two Groups The observation group showed significantly improved overall glycemic control compared with the control group, as reflected by CGMS-derived metrics.. TIR was higher, and TAR was lower in the observation group ( P = 0.007 and P = 0.005, respectively), whereas no significant difference was observed in TBR. Glycemic variability was reduced, as indicated by significantly lower MODD, MG, SD, and CV (all P ≤ 0.003), while LAGE and MAGE did not differ significantly between groups. The time to achieve target blood glucose levels was significantly shorter, and the total daily insulin dose at the end of treatment was lower in the observation group ( P < 0.001 and P = 0.03, respectively). In addition, the rate of achieving good glycemic control was significantly higher in the observation group ( P = 0.001). Although the incidences of mild and severe hypoglycemia were numerically lower in the observation group, these differences were not statistically significant, and no significant difference in adverse events was observed between groups. (Table 3 )(Fig. 2 ). Table 3 Glycemic excursion parameters, insulin dosage, and adverse reactions at the end of the two treatment groups Clinical Features Control group (n = 63) Observation group (n = 63) P -value TIR(%) 74.67 ± 22.03 84.03 ± 15.36 0.007 TAR(%) 22.14 ± 20.86 13.59 ± 11.32 0.005 TBR(%) 1.59 ± 2.84 0.98 ± 2.26 0.187 LAGE (mmol/L) 8.78 ± 2.84 8.17 ± 2.20 0.185 MAGE (mmol/L) 5.41 ± 2.05 5.04 ± 1.69 0.277 MODD (mmol/L) 2.47 ± 0.88 1.84 ± 0.74 <0.001 MG (mmol/L) 9.74 ± 1.77 8.26 ± 1.41 <0.001 SD (mmol/L) 3.47 ± 0.74 2.74 ± 0.72 <0.001 CV(%) 35.62 ± 5.83 32.42 ± 6.08 0.003 Time to Achieve Target Blood Glucose Level(days) 5.0 ± 1.8 3.1 ± 1.7 <0.001 Total insulin dose at end of treatment(U/kg/day) 41.59 ± 9.45 37.95 ± 9.13 0.03 Mild hypoglycemia (≤ 3.9 mmol/L) 28(44.4%) 19(30.2%) 0.097 Severe hypoglycemia (≤ 3.0 mmol/L) 9(14.3%) 3(4.8%) 0.069 Rate of Achieving Good Glycemic Control(%) 23(36.5%) 41(65.1%) 0.001 Gastrointestinal reactions and other adverse events (n) 3(37.5%) 5(62.5%) 0.359 Note: TIR: Time in Range for glucose; TAR: Time Above Range; TBR: Time Below Range; LAGE: Maximum Amplitude of Glucose Excursion; MAGE: Mean Amplitude of Glucose Excursion; MODD: Mean Daily Glucose Deviation; MG: Mean Glucose; SD: Standard Deviation of Glucose; CV: Coefficient of Variation Discussion Currently, the duration of intensive insulin therapy for severe hyperglycemia has gradually evolved from the initial 3-month period to shorter intervals (2 weeks to 3 months). However, within China's Diagnosis-Related Groups (DRG) framework, exploring a 1-week intensive insulin therapy regimen holds practical significance. This study compared the efficacy differences between intensive hypoglycemic therapy with IDegLira combined with insulin aspart versus insulin glargine combined with insulin aspart over a 1-week period in overweight/obese patients with T2DM. Research findings indicate that IDegLira, combined with aspart insulin, achieves high-quality glycemic control more rapidly than glargine insulin combined with aspart insulin. It demonstrates significant advantages in glycemic stability, improvement of pancreatic function, and insulin dose savings, suggesting its important clinical application value in short-term intensive therapy. The effectiveness and stability of blood glucose control are key objectives in the management of T2DM. Significant fluctuations in blood glucose levels among overweight/obese patients can further exacerbate insulin resistance, impair vascular endothelial function, and increase the risk of long-term cardiovascular events. 4 , 5 , 13 TIR is considered a key indicator reflecting the quality of glycemic control and shows a significant negative correlation with the risk of diabetic microvascular complications. 14 , 15 This study demonstrated that the TIR rate in the IDegLira group reached 84.03%, significantly higher than the 74.67% observed in the insulin glargine group ( P < 0.05). Simultaneously, the TAR, MODD, CV, and SD values in the IDegLira group showed significant reductions, indicating that this regimen not only offers superior overall glycemic control but also markedly reduces intraday and diurnal blood glucose fluctuations, thereby achieving more stable glycemic management. Malighetti et al. 16 demonstrated in the TiREX study that IDegLira significantly increased TIR (56.8%→81.3%) and markedly reduced TAR (42.3%→17.1%) in the short term, suggesting dual benefits in improving hyperglycemic exposure and enhancing target achievement rates. Philis-Tsimikas et al. 17 further demonstrated that IDegLira significantly outperformed insulin glargine U100 in improving TIR. This advantage in TIR may be related to the ultra-long and stable basal insulin profile of IDegLira. Insulin degludec ensures sustained 24-hour basal glucose control with minimal intraday variability, thereby reducing periods of hyperglycemic exposure. In contrast, the pharmacodynamic profile of insulin glargine is associated with relatively greater post-injection fluctuations, which may compromise the stability of fasting and early morning glycemic control. 18 In contrast, glargine insulin primarily acts on basal blood glucose levels and has limited capacity to regulate postprandial fluctuations. 19 Furthermore, the study demonstrated that the MG level in the IDegLira group was significantly lower than that in the control group (8.26 vs 9.74 mmol/L, P < 0.05), further confirming its ability to enhance glycemic control while better maintaining glucose homeostasis. The findings of this study not only align with the ADA guidelines principle that "glycemic management requires balancing target achievement with stability", 20 but also support that the combination of GLP-1RA with basal insulin reduces glycemic variability, potentially offering cardiovascular and metabolic protective effects. 21 Impaired pancreatic β-cell function and insulin resistance constitute the core pathological basis in overweight/obese T2DM patients. Therefore, improving pancreatic function and alleviating insulin resistance are crucial for optimizing long-term prognosis. 3 , 22 A treatment study in elderly patients with T2DM demonstrated a significant reduction in the insulin resistance index after 6 months of treatment with IDegLira (from 42.39 to 32.84, P < 0.0001). 23 In this study, the IDegLira group demonstrated a reduction in HOMA-IR-CP after one week of treatment, with levels falling below those of the control group, consistent with previous reports. 24 In a 26-week open-label trial, Holst et al. demonstrated that IDegLira enhances endogenous insulin secretion and improves β-cell function. 25 Our findings also indicate that the IDegLira group demonstrated an improvement in HOMA-islet-CPDM in the short term. This early improvement may be primarily attributable to liraglutide-induced glucose-dependent insulin secretion enhancement and glucagon release inhibition, along with reduced hepatic glucose output and improved peripheral insulin sensitivity, rather than long-term structural changes in β-cell mass or differentiation. In contrast, glargine insulin primarily supplements basal insulin and lacks direct protective effects on pancreatic function. 26 – 28 Furthermore, several previous studies have demonstrated that IDegLira reduces insulin dosage compared with IGlar U100 or degludec insulin. 26 , 29 , 30 This study found that the daily total insulin dose was lower in the IDegLira group (37.95 U/d vs 41.59 U/d). This outcome demonstrates that Ideglirase not only exhibits superior glycemic control efficacy but also helps mitigate the risk of weight gain associated with increased insulin dosing, aligning with the clinical strategy of "coordinated management of glycemic control and body weight". 31 Therefore, for individuals with severe hyperglycemia and overweight/obesity in T2DM, selecting IDegLira over glargine insulin combined with rapid-acting insulin for short-term intensive insulin therapy can reduce blood glucose levels while also alleviating insulin resistance and improving pancreatic function. Notably, the observation group achieved glycemic control significantly faster (3.1 ± 1.7 days vs.5.0 ± 1.8 days, P < 0.001), and the rate of achieving the composite primary endpoint was nearly double that of the control group(65.1%vs.36.5%). Against the backdrop of current DIP/DRG cost containment and efforts to shorten hospital stays, achieving rapid, safe, and high-quality compliance within a short timeframe holds significant clinical importance. 32 CGMS ensured the accuracy of glucose fluctuation assessment in this study, overcoming the limitations of traditional fingerstick glucose monitoring in capturing the full dynamics of blood glucose changes during short-term treatment. 33 This also provides an objective basis for evaluating future short-term intensive insulin therapy regimens. This study has certain limitations that require refinement in subsequent research: First, the sample was limited to a single center. Future studies could conduct multicenter collaborative research, incorporating patients from different regions and hospitals to enhance sample representativeness. Second, the observation period was only 7 days; a follow-up study lasting 2 weeks to 3 months could be designed to further validate the efficacy of the protocol. Third, no subgroup analysis was conducted for different BMI strata (e.g., BMI 24–28 kg/m², BMI ≥ 28 kg/m²). Future studies should refine stratification to explore individualized intensive glucose-lowering strategies. In summary, the combination of IDegLira with aspart insulin for overweight/obese patients with T2DM enables faster and more stable glycemic control. This approach reduces insulin dosage while effectively improving pancreatic function, and overweight/obese T2DM patients enables faster and smoother glycemic control. It effectively improves pancreatic function and reduces insulin resistance while decreasing insulin dosage, with a favorable safety profile. This regimen demonstrates superiority over the traditional insulin glargine combination therapy and is recommended as the preferred short-term intensive treatment option for this patient population. Declarations Funding This study received no funding support. Competing Interests The authors claim no conflict of interest in this study Author Contributions Yaping Sun and Liwu Xu jointly designed the study and developed the protocol. Yaping Sun collected and analyzed the data and drafted the initial manuscript. Xiaolei Li assisted with statistical analysis and the preparation of figures and tables. Liwu Xu provided critical revisions to multiple versions of the manuscript. As the corresponding author, Liwu Xu assumes full responsibility for the integrity of the data, the accuracy of the analysis, and the work as a whole. Ethics Review and Institutional Affiliation The study was approved by the Medical Ethics Committee of the First Hospital of Anhui University of Science and Technology (Ethics Approval No.2025-KY-Y026-001) and and is in accordance with the Declaration of Helsinki and registered with the China Clinical Trial Center. Consent to participate Informed consent was obtained from all individual participants included in the study. References International Diabetes Federation(IDF), IDF Diabetes Atlas , 10th edn. (International Diabetes Federation(IDF), Brussels, 2022) M.G. Tinajero, V.S. Malik, An Update on the Epidemiology of Type 2 Diabetes: A Global Perspective. Endocrinol. Metab. Clin. North. Am. 50 (3), 337–355 (2021) R. Ruze, T. Liu, X. Zou et al., Obesity and type 2 diabetes mellitus: connections in epidemiology, pathogenesis, and treatments. Front. Endocrinol. (Lausanne). 14 , 1161521 (2023) M.P. Czech, Mechanisms of insulin resistance related to white, beige, and brown adipocytes. Mol. 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Barnett, IDegLira: combining efficacy, durability, and convenience? Lancet Diabetes Endocrinol. 7 (8), 584–585 (2019) American Diabetes Association Professional Practice Committee, 8. Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes: Standards of Care in Diabetes-2025. Diabetes Care. 48 (1 Suppl 1), S167–S180 (2025) H. Yao, A. Zhang, D. Li et al., Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis. BMJ. 384 , e076410 (2024) F.P. Bautista, G. Jr Jasul, O.A. Dampil, Insulin Resistance and β-Cell Function of Lean versus Overweight or Obese Filipino Patients with Newly Diagnosed Type 2 Diabetes Mellitus. J. ASEAN Fed. Endocr. Soc. 34 (2), 164–170 (2019) F. Mancinetti, D. Xenos, De M. Fano et al., Switching from insulin injections to degludec/liraglutide in older frail persons: 6-month body composition remodelling. Eur. Geriatr. Med. 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Gouet et al., Insulin degludec/liraglutide (IDegLira) maintains glycaemic control and improves clinical outcomes, regardless of pre-trial insulin dose, in people with type 2 diabetes that is uncontrolled on basal insulin. Diabet. Med. 37 (2), 267–276 (2020) Z.J. Taybani, B. Bótyik, A. Gyimesi, M. Katkó, T. Várkonyi, One-year safety and efficacy results of insulin treatment simplification with IDegLira in type 2 diabetes. Endocrinol. Diabetes Metab. 6 (1), e390 (2023) L.K. Billings, A. Doshi, D. Gouet et al., Efficacy and Safety of IDegLira Versus Basal-Bolus Insulin Therapy in Patients With Type 2 Diabetes Uncontrolled on Metformin and Basal Insulin: The DUAL VII Randomized Clinical Trial. Diabetes Care. 41 (5), 1009–1016 (2018) H.E. Bays, S. Bindlish, T.L. Clayton, Obesity, diabetes mellitus, and cardiometabolic risk: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2023. Obes. Pillars. 5 , 100056 (2023) X. Wang, Y. Tao, S. Gao et al., Effects of DRG/DIP payment reform on hospital pharmacy administration and pharmaceutical services in China: a multicenter cross-sectional study. Front. Public. Health. 13 , 1585279 (2025) T. Battelino, C.M. Alexander, S.A. Amiel et al., Continuous glucose monitoring and metrics for clinical trials: an international consensus statement. Lancet Diabetes Endocrinol. 11 (1), 42–57 (2023) Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 01 May, 2026 Reviews received at journal 30 Apr, 2026 Reviewers agreed at journal 19 Apr, 2026 Reviewers invited by journal 29 Mar, 2026 Editor assigned by journal 21 Feb, 2026 Submission checks completed at journal 21 Feb, 2026 First submitted to journal 19 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8921856","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":614844432,"identity":"18c099c6-22ad-4981-a5b1-a6f2fa50d097","order_by":0,"name":"yaping sun","email":"","orcid":"","institution":"Bengbu Medical University","correspondingAuthor":false,"prefix":"","firstName":"yaping","middleName":"","lastName":"sun","suffix":""},{"id":614844433,"identity":"54e274e6-c3bc-420b-96ec-52c6e0dd7a15","order_by":1,"name":"Xiaolei Li","email":"","orcid":"","institution":"The First Hospital of Anhui University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Xiaolei","middleName":"","lastName":"Li","suffix":""},{"id":614844434,"identity":"ea7fcc15-afc0-4842-90d8-00e925e15f1a","order_by":2,"name":"Liwu Xu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIiWNgGAWjYDACdjApIcfP3nzgwIcKYrQwg0kLY8meY4kHZ5whXktF4oYbOcaHeVuI0GFwmMf4M2+bROKGM2c+HOBtYJDnFzuAX4tkM4+BMc8ZCeOZx3s3HJDcwWA4c3YCfi38zLwbknkqJGT7zpzdcMDwDEOCwW0CWtiAWg7zGEgwNtzIeXAgsY0ILUBbNjYDbVGccCOH4cBBYrRINvN/ZpwD9AswkA0ONpyRIOwXg+NtyR/ettWBovLx5z8VNvL80gS0gAATD4ItQVg5CDD+IE7dKBgFo2AUjFQAAAvtSOGUp8lJAAAAAElFTkSuQmCC","orcid":"","institution":"The First Hospital of Anhui University of Science and Technology","correspondingAuthor":true,"prefix":"","firstName":"Liwu","middleName":"","lastName":"Xu","suffix":""}],"badges":[],"createdAt":"2026-02-20 03:08:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8921856/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8921856/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105982436,"identity":"e9ac6e7b-65a1-413a-bd07-742fa0eaf265","added_by":"auto","created_at":"2026-04-02 07:00:53","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":191174,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of FPG, HOMA-IR, and HOMA-islet-CPDM Levels and Their Changes Before and After Treatment Between the Two Groups. (a) Changes in FPG from baseline to post-treatment in both groups. (b) Changes in HOMA-IR from baseline to post-treatment in both groups. (c) Changes in HOMA-islet-CPDM from baseline to post-treatment in both groups. (d) Between-group comparison of ΔFPG. (e) Between-group comparison of ΔHOMA-IR. (f) Between-group comparison of ΔHOMA-islet-CPDM. FPG: Fasting Plasma Glucose; HOMA-IR-CP: C-peptide Insulin Resistance Index; HOMAislet-CPDM: C-peptide Islet Function Index\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8921856/v1/7e4764ad8768d6f0bbe38790.png"},{"id":105982435,"identity":"63cc00b0-cfdc-4f32-bdde-1b8879923f50","added_by":"auto","created_at":"2026-04-02 07:00:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":189609,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of glycemic control, variability, and treatment efficiency between the two treatment groups. (h) Comparison of TAR between the two groups. (i) Comparison of MG between the two groups. (j) Comparison of TIR between the two groups. (k) Comparison of SD between the two groups. (l) Comparison of CV between the two groups. (m) Comparison of time to achieve glycemic targets between the two groups. (n) Comparison of daily total insulin dose between the two groups. (o) Comparison of the proportions of patients meeting and not meeting glycemic targets between the two groups. TIR: Time in Range for glucose; TAR: Time Above Range; MODD: Mean Daily Glucose Deviation; MG: Mean Glucose; SD: Standard Deviation of Glucose; CV: Coefficient of Variation\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8921856/v1/438f5feb43ae086ad395dce1.png"},{"id":106401855,"identity":"beeef6f0-203b-4847-8f46-c0581e5246c5","added_by":"auto","created_at":"2026-04-08 09:10:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1031236,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8921856/v1/4e8fa4ae-003b-44bb-83ea-f18331d2f239.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparative Analysis of IDegLira versus Insulin Glargine in Short-Term Intensive Therapy for Overweight or Obese Patients with Type 2 Diabetes Mellitus","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe latest data from the International Diabetes Federation (IDF) indicate that 537\u0026nbsp;million adults worldwide currently have diabetes, and this number is projected to increase to 643\u0026nbsp;million by 2030.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Overweight and obesity are prominent features among individuals with T2DM globally, affecting approximately 85% of patients.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Studies have shown that visceral fat accumulation is associated with insulin resistance and represents one of the major risk factors for the development of this disease.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Overweight and obesity increase the difficulty of blood glucose control in diabetic patients and elevate the risk of cardiovascular disease, while early intensive glycemic control can reduce the metabolic memory effect of vascular complications.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e In overweight or obese patients with T2DM, treatment strategies should address not only glycemic control but also weight reduction and the improvement of insulin resistance.\u003c/p\u003e \u003cp\u003eShort-term intensive insulin therapy is an effective approach for patients with T2DM presenting with severe hyperglycemia.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e The current standard intensive insulin therapy typically involves either continuous subcutaneous insulin infusion with short-or rapid-acting insulin or a regimen of preprandial short-or rapid-acting insulin combined with insulin glargine; however, this approach is often less effective in overweight or obese patients with T2DM who exhibit marked insulin resistance.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e The 2022 American Diabetes Association (ADA) Standards of Care state that for patients with T2DM inadequately controlled on basal insulin and oral antihyperglycemic agents, a basal insulin\u0026ndash;GLP-1 receptor agonist (GLP-1 RA) injection may be considered as a treatment option.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e In 2016, the U.S.Food and Drug Administration (FDA) approved the basal insulin GLP-1 receptor agonist injection\u0026mdash;IDegLira\u0026mdash;for the treatment of diabetes.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e This study aimed to evaluate the short-term intensive effects of IDegLira versus insulin glargine, each combined with insulin aspart, in overweight or obese patients with T2DM, with the goal of exploring novel strategies for short-term insulin-based glycemic management in this population.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eResearch subjects\u003c/h2\u003e \u003cp\u003eA total of 126 eligible overweight or obese patients with T2DM hospitalized in the Endocrinology Department between October 2024 and June 2025 were randomly assigned in a 1:1 ratio to the control group (n\u0026thinsp;=\u0026thinsp;63) or observation group (n\u0026thinsp;=\u0026thinsp;63).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eInclusion, exclusion, and grouping criteria\u003c/h3\u003e\n\u003cp\u003eInclusion Criteria: (1) Met the diagnostic and classification criteria for T2DM; (2) Had glycated hemoglobin (HbA1c)\u0026thinsp;\u0026ge;\u0026thinsp;9.0% or fasting plasma glucose (FPG)\u0026thinsp;\u0026ge;\u0026thinsp;11.1 mmol/L; (3) Had a body mass index (BMI)\u0026thinsp;\u0026ge;\u0026thinsp;24 kg/m\u0026sup2; or a waist circumference\u0026thinsp;\u0026gt;\u0026thinsp;90 cm in males and \u0026gt;\u0026thinsp;85 cm in females; (4) Were aged between 18 and 80 years; (5) The patient and family members were informed about the study and had signed the consent form.\u003c/p\u003e \u003cp\u003eExclusion Criteria: (1) Had severe infection or acute complications of diabetes; (2) Had severe heart, liver, or kidney failure; (3) Were pregnant, breastfeeding, or trying to conceive; (4) Were allergic to the drugs used in this study; (5) Had sarcopenia, medullary thyroid carcinoma (including a personal or family history), or multiple endocrine neoplasia type 2. (6) Patients with severe non-proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) were excluded.\u003c/p\u003e\n\u003ch3\u003eTreatment Methods\u003c/h3\u003e\n\u003cp\u003eEligible patients were randomly assigned to the control or observation group in a 1:1 ratio using a random number table, and intensive therapy was administered for 1 week.\u003c/p\u003e \u003cp\u003ePatients in the observation group received preprandial subcutaneous injections of insulin aspart (Novo Nordisk, 3 mL:300 U) combined with once-daily subcutaneous injections of IDegLira (Novo Nordisk, 3 mL containing 300 U insulin degludec and 10.8 mg liraglutide). Patients in the control group received preprandial subcutaneous injections of insulin aspart combined with once-daily subcutaneous injections of insulin glargine (Sanofi-Aventis Deutschland GmbH, 1.5 mL:450 U per prefilled pen, 300U/ml).\u003c/p\u003e \u003cp\u003eThe initial total insulin dose in both the observation and control groups was 0.5 U/(kg\u0026middot;d). The starting dose of insulin glargine or IDegLira constituted 50% of the total dose, with the remaining 50% distributed equally among the three pre-meal doses of insulin aspart at a ratio of 1:1:1. The starting dose of IDegLira did not exceed 16 units in principle, with a maximum dose not exceeding 50 units. Dosage was adjusted based on fasting blood glucose (FBG) levels: when FBG was \u0026gt;\u0026thinsp;7.8 mmol/L, the dose was increased by 4 U; when 6.1 mmol/L\u0026thinsp;\u0026le;\u0026thinsp;FBG\u0026thinsp;\u0026le;\u0026thinsp;7.8 mmol/L, the dose was increased by 2 U; when 4.4 mmol/L\u0026thinsp;\u0026le;\u0026thinsp;FBG\u0026thinsp;\u0026lt;\u0026thinsp;6.1 mmol/L, no adjustment was made; when FBG was \u0026lt;\u0026thinsp;4.4 mmol/L, the dose was reduced by 2 U. The method for adjusting the initial dose of insulin glargine in the control group was the same as described above. Pre-meal insulin doses were adjusted as needed based on pre-meal blood glucose levels before the next meal, with dose adjustments performed every 2\u0026ndash;3 days.\u003c/p\u003e \u003cp\u003eAll participants in both groups received the same standardized lifestyle management and education program, including dietary and exercise counseling. Both groups were equipped with the same continuous glucose monitoring system (manufacturer: Shenzhen Silicon-based Sensor Technology Co., Ltd.; model: GS1-10).\u003c/p\u003e\n\u003ch3\u003eData Collection\u003c/h3\u003e\n\u003cp\u003eOn the first day of hospitalization, clinical and laboratory data were collected, including age, sex, height, weight, BMI, duration of type 2 diabetes, FPG, glycated hemoglobin (HbA1c), fasting C-peptide (FCP), and adiponectin (APN). On day 7 of treatment, the achievement of the composite endpoint for high-quality glycemic control was assessed, which required patients to meet all three of the following criteria: (1) efficacy: TIR\u0026thinsp;\u0026gt;\u0026thinsp;70%; (2) stability: CV\u0026thinsp;\u0026lt;\u0026thinsp;36%; and (3) safety: no hypoglycemic events (3.0 mmol/L). Hypoglycemia, gastrointestinal symptoms, and other adverse events were recorded, along with total daily insulin dose on the final day(U/kg/day), FCP, and APN levels. C-peptide\u0026ndash;based indices of insulin resistance (HOMA-IR-CP) and β-cell function (HOMA islet-CPDM) were calculated before and after treatment using FCP, according to the following formulas:\u003c/p\u003e \u003cp\u003eHOMA-IR-CP\u0026thinsp;=\u0026thinsp;1.5\u0026thinsp;+\u0026thinsp;FPG\u0026times;FCP/2800;\u003c/p\u003e \u003cp\u003eHOMA islet-CPDM\u0026thinsp;=\u0026thinsp;0.27\u0026times;FCP/(FPG\u0026thinsp;\u0026minus;\u0026thinsp;3.5)\u003csup\u003e11,12\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe CGMS sensor kit was used for a 7-day monitoring period. The glycemic target in the reports was set at 3.9\u0026ndash;10.0 mmol/L. Observed indicators included TIR, TAR, time below range (TBR; 3.9 mmol/L or \u0026lt;\u0026thinsp;2.9 mmol/L), largest amplitude of glucose excursion (LAGE), mean amplitude of glycemic excursions (MAGE), MODD, MG, SD, and CV.\u003c/p\u003e\n\u003ch3\u003eStatistical Methods\u003c/h3\u003e\n\u003cp\u003eStatistical analysis was performed using SPSS version 26.0 (SPSS Inc., Chicago, IL, USA) and Prism software (GraphPad, version 10.6.0). Continuous variables with a normal distribution were expressed as mean\u0026plusmn;standard deviation(Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD) and analyzed using the t-test or analysis of variance(ANOVA). Non-normally distributed data were presented as median with interquartile range and compared using nonparametric tests (Mann-Whitney U). Categorical variables were expressed as frequency (n) and percentage and analyzed using the chi-square test. Paired t-tests were used to compare pre-and post-treatment parameters within groups. Fisher's exact test was applied when appropriate. Two-sided \u003cem\u003eP\u003c/em\u003e-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant.\u003c/p\u003e "},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003eComparison of Baseline Characteristics Between the Two Patient Groups\u003c/h2\u003e \u003cp\u003eThere were no significant differences between the two groups in baseline characteristics, including age, sex, BMI, HbA1c, and duration of type 2 diabetes, as well as metabolic and islet function parameters (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline Characteristics of Randomized Participants\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical Data\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;63)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eObservation group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;63)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender (Male: Female)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33: 30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36: 27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.591\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge(years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58.48\u0026thinsp;\u0026plusmn;\u0026thinsp;1.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55.81\u0026thinsp;\u0026plusmn;\u0026thinsp;1.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of illness (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(3,6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(3,5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.739\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.57(25.95, 30.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.99(25.97, 30.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.610\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHbA1c(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.2(8.67,11.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.1(8.9,11.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.639\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFPG(mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.6(8.1,13.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.1(8.2,13.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.874\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFCP (pmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e440.23(271.42,562.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e486.57(347.55,662.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.127\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPN(mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.79(4.4,9.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.0(5.2,11.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.857\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHOMA-IR-CP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.19(2.65,3.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.47(2.75,4.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.273\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHOMAislet-CPDM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.08(10.43,25.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.28(13.11,29.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.134\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eNote: BMI: Body mass index; FPG: Fasting Plasma Glucose; FCP: Fasting C-peptide; APN: Adiponectin; HOMA-IR-CP: C-peptide Insulin Resistance Index; HOMAislet-CPDM: C-peptide Islet Function Index\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e\n\u003ch3\u003eComparison of Post-treatment Metabolic and Islet Function Parameters Between the Two Groups\u003c/h3\u003e\n\u003cp\u003eAfter 7 days of treatment, there were no significant differences between the two groups in APN, FCP, or their corresponding change values (Δ)(\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). In contrast, significant differences were observed between the two groups in FPG, HOMA-islet-CPDM, and their changes (Δ) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Post-treatment FPG in the observation group was significantly lower than that in the control group [5.2(5.0-5.5) mmol/L vs.7.5(6.6\u0026ndash;8.4) mmol/L, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001], and the decrease in FPG (ΔFPG) was also markedly greater [4.7(3-8.7) mmol/L vs.2.9(0.4\u0026ndash;5.8) mmol/L, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001]. HOMA-islet-CPDM increased significantly in the observation group[73.28(44.05-100.09)vs.25.08(15.79\u0026ndash;38.73), \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001], and its change value (Δ) was also higher than that in the control group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), indicating a more pronounced improvement in β-cell function. A significantly greater reduction in HOMA-IR-CP was observed in the observation group compared with the control group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005), despite comparable post-treatment levels between groups, indicating a more pronounced improvement in insulin resistance (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of Post-treatment Metabolic and Islet Function Parameters Between the Two Groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical Data\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;63)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eObservation group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;63)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eFPG (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.5(6.6,8.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.2(5.0,5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;0.001\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e--△Change\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.9(0.4,5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.7(3,8.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eAPN (mg/L)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.4(4.7,10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.3(5.2,10.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.547\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e--△Change\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.05(-0.6,0.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.1(-0.7,0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.914\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eFCP (pmol/L)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e364.10(231.70,589.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e446.85(258.18,628.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.162\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e--△Change\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36.41(-72.82,139.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.17(-86.06,175.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eHOMA-IR-CP\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.51(2.08,3.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.36(1.96, 2.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.104\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e--△Change\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.60(-0.05,1.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.98(0.41,1.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eHOMA islet-CPDM\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.08(15.79,38.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73.28(44.05,100.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e--△Change\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.18(-1.79,16.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46.98(27.73,77.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eNote: FPG: Fasting Plasma Glucose; FCP: Fasting C-peptide; APN: Adiponectin; HOMA-IR-CP: C-peptide Insulin Resistance Index; HOMAislet-CPDM: C-peptide Islet Function Index\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eComparison of CGMS Metrics Between the Two Groups\u003c/h2\u003e \u003cp\u003eThe observation group showed significantly improved overall glycemic control compared with the control group, as reflected by CGMS-derived metrics.. TIR was higher, and TAR was lower in the observation group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007 and \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005, respectively), whereas no significant difference was observed in TBR. Glycemic variability was reduced, as indicated by significantly lower MODD, MG, SD, and CV (all \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;0.003), while LAGE and MAGE did not differ significantly between groups. The time to achieve target blood glucose levels was significantly shorter, and the total daily insulin dose at the end of treatment was lower in the observation group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001 and \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.03, respectively). In addition, the rate of achieving good glycemic control was significantly higher in the observation group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001). Although the incidences of mild and severe hypoglycemia were numerically lower in the observation group, these differences were not statistically significant, and no significant difference in adverse events was observed between groups. (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)(Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eGlycemic excursion parameters, insulin dosage, and adverse reactions at the end of the two treatment groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical Features\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;63)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eObservation group (n\u0026thinsp;=\u0026thinsp;63)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTIR(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74.67\u0026thinsp;\u0026plusmn;\u0026thinsp;22.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84.03\u0026thinsp;\u0026plusmn;\u0026thinsp;15.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAR(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.14\u0026thinsp;\u0026plusmn;\u0026thinsp;20.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.59\u0026thinsp;\u0026plusmn;\u0026thinsp;11.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTBR(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.59\u0026thinsp;\u0026plusmn;\u0026thinsp;2.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.98\u0026thinsp;\u0026plusmn;\u0026thinsp;2.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.187\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLAGE (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.78\u0026thinsp;\u0026plusmn;\u0026thinsp;2.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.17\u0026thinsp;\u0026plusmn;\u0026thinsp;2.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.185\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMAGE (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.41\u0026thinsp;\u0026plusmn;\u0026thinsp;2.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.04\u0026thinsp;\u0026plusmn;\u0026thinsp;1.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.277\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMODD (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.84\u0026thinsp;\u0026plusmn;\u0026thinsp;0.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMG (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.74\u0026thinsp;\u0026plusmn;\u0026thinsp;1.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.26\u0026thinsp;\u0026plusmn;\u0026thinsp;1.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSD (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCV(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35.62\u0026thinsp;\u0026plusmn;\u0026thinsp;5.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.42\u0026thinsp;\u0026plusmn;\u0026thinsp;6.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime to Achieve Target Blood Glucose Level(days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal insulin dose at end of treatment(U/kg/day)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41.59\u0026thinsp;\u0026plusmn;\u0026thinsp;9.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.95\u0026thinsp;\u0026plusmn;\u0026thinsp;9.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMild hypoglycemia (\u0026le;\u0026thinsp;3.9 mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28(44.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19(30.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.097\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere hypoglycemia (\u0026le;\u0026thinsp;3.0 mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(14.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(4.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.069\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRate of Achieving Good Glycemic Control(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23(36.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41(65.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal reactions and other adverse events (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(37.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(62.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.359\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eNote: TIR: Time in Range for glucose; TAR: Time Above Range; TBR: Time Below Range; LAGE: Maximum Amplitude of Glucose Excursion; MAGE: Mean Amplitude of Glucose Excursion; MODD: Mean Daily Glucose Deviation; MG: Mean Glucose; SD: Standard Deviation of Glucose; CV: Coefficient of Variation\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eCurrently, the duration of intensive insulin therapy for severe hyperglycemia has gradually evolved from the initial 3-month period to shorter intervals (2 weeks to 3 months). However, within China's Diagnosis-Related Groups (DRG) framework, exploring a 1-week intensive insulin therapy regimen holds practical significance. This study compared the efficacy differences between intensive hypoglycemic therapy with IDegLira combined with insulin aspart versus insulin glargine combined with insulin aspart over a 1-week period in overweight/obese patients with T2DM. Research findings indicate that IDegLira, combined with aspart insulin, achieves high-quality glycemic control more rapidly than glargine insulin combined with aspart insulin. It demonstrates significant advantages in glycemic stability, improvement of pancreatic function, and insulin dose savings, suggesting its important clinical application value in short-term intensive therapy.\u003c/p\u003e \u003cp\u003eThe effectiveness and stability of blood glucose control are key objectives in the management of T2DM. Significant fluctuations in blood glucose levels among overweight/obese patients can further exacerbate insulin resistance, impair vascular endothelial function, and increase the risk of long-term cardiovascular events.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e TIR is considered a key indicator reflecting the quality of glycemic control and shows a significant negative correlation with the risk of diabetic microvascular complications.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e This study demonstrated that the TIR rate in the IDegLira group reached 84.03%, significantly higher than the 74.67% observed in the insulin glargine group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Simultaneously, the TAR, MODD, CV, and SD values in the IDegLira group showed significant reductions, indicating that this regimen not only offers superior overall glycemic control but also markedly reduces intraday and diurnal blood glucose fluctuations, thereby achieving more stable glycemic management. Malighetti et al.\u003csup\u003e16\u003c/sup\u003e demonstrated in the TiREX study that IDegLira significantly increased TIR (56.8%\u0026rarr;81.3%) and markedly reduced TAR (42.3%\u0026rarr;17.1%) in the short term, suggesting dual benefits in improving hyperglycemic exposure and enhancing target achievement rates. Philis-Tsimikas et al.\u003csup\u003e17\u003c/sup\u003e further demonstrated that IDegLira significantly outperformed insulin glargine U100 in improving TIR. This advantage in TIR may be related to the ultra-long and stable basal insulin profile of IDegLira. Insulin degludec ensures sustained 24-hour basal glucose control with minimal intraday variability, thereby reducing periods of hyperglycemic exposure. In contrast, the pharmacodynamic profile of insulin glargine is associated with relatively greater post-injection fluctuations, which may compromise the stability of fasting and early morning glycemic control.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e In contrast, glargine insulin primarily acts on basal blood glucose levels and has limited capacity to regulate postprandial fluctuations.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Furthermore, the study demonstrated that the MG level in the IDegLira group was significantly lower than that in the control group (8.26 vs 9.74 mmol/L, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), further confirming its ability to enhance glycemic control while better maintaining glucose homeostasis. The findings of this study not only align with the ADA guidelines principle that \"glycemic management requires balancing target achievement with stability\",\u003csup\u003e20\u003c/sup\u003e but also support that the combination of GLP-1RA with basal insulin reduces glycemic variability, potentially offering cardiovascular and metabolic protective effects.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e Impaired pancreatic β-cell function and insulin resistance constitute the core pathological basis in overweight/obese T2DM patients. Therefore, improving pancreatic function and alleviating insulin resistance are crucial for optimizing long-term prognosis.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e A treatment study in elderly patients with T2DM demonstrated a significant reduction in the insulin resistance index after 6 months of treatment with IDegLira (from 42.39 to 32.84, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001).\u003csup\u003e23\u003c/sup\u003e In this study, the IDegLira group demonstrated a reduction in HOMA-IR-CP after one week of treatment, with levels falling below those of the control group, consistent with previous reports.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e In a 26-week open-label trial, Holst et al. demonstrated that IDegLira enhances endogenous insulin secretion and improves β-cell function.\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e Our findings also indicate that the IDegLira group demonstrated an improvement in HOMA-islet-CPDM in the short term. This early improvement may be primarily attributable to liraglutide-induced glucose-dependent insulin secretion enhancement and glucagon release inhibition, along with reduced hepatic glucose output and improved peripheral insulin sensitivity, rather than long-term structural changes in β-cell mass or differentiation. In contrast, glargine insulin primarily supplements basal insulin and lacks direct protective effects on pancreatic function.\u003csup\u003e\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e Furthermore, several previous studies have demonstrated that IDegLira reduces insulin dosage compared with IGlar U100 or degludec insulin.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e,\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e This study found that the daily total insulin dose was lower in the IDegLira group (37.95 U/d vs 41.59 U/d). This outcome demonstrates that Ideglirase not only exhibits superior glycemic control efficacy but also helps mitigate the risk of weight gain associated with increased insulin dosing, aligning with the clinical strategy of \"coordinated management of glycemic control and body weight\".\u003csup\u003e31\u003c/sup\u003e Therefore, for individuals with severe hyperglycemia and overweight/obesity in T2DM, selecting IDegLira over glargine insulin combined with rapid-acting insulin for short-term intensive insulin therapy can reduce blood glucose levels while also alleviating insulin resistance and improving pancreatic function.\u003c/p\u003e \u003cp\u003eNotably, the observation group achieved glycemic control significantly faster (3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7 days vs.5.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8 days, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and the rate of achieving the composite primary endpoint was nearly double that of the control group(65.1%vs.36.5%). Against the backdrop of current DIP/DRG cost containment and efforts to shorten hospital stays, achieving rapid, safe, and high-quality compliance within a short timeframe holds significant clinical importance.\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e CGMS ensured the accuracy of glucose fluctuation assessment in this study, overcoming the limitations of traditional fingerstick glucose monitoring in capturing the full dynamics of blood glucose changes during short-term treatment.\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e This also provides an objective basis for evaluating future short-term intensive insulin therapy regimens.\u003c/p\u003e \u003cp\u003eThis study has certain limitations that require refinement in subsequent research: First, the sample was limited to a single center. Future studies could conduct multicenter collaborative research, incorporating patients from different regions and hospitals to enhance sample representativeness. Second, the observation period was only 7 days; a follow-up study lasting 2 weeks to 3 months could be designed to further validate the efficacy of the protocol. Third, no subgroup analysis was conducted for different BMI strata (e.g., BMI 24\u0026ndash;28 kg/m\u0026sup2;, BMI\u0026thinsp;\u0026ge;\u0026thinsp;28 kg/m\u0026sup2;). Future studies should refine stratification to explore individualized intensive glucose-lowering strategies.\u003c/p\u003e \u003cp\u003eIn summary, the combination of IDegLira with aspart insulin for overweight/obese patients with T2DM enables faster and more stable glycemic control. This approach reduces insulin dosage while effectively improving pancreatic function, and overweight/obese T2DM patients enables faster and smoother glycemic control. It effectively improves pancreatic function and reduces insulin resistance while decreasing insulin dosage, with a favorable safety profile. This regimen demonstrates superiority over the traditional insulin glargine combination therapy and is recommended as the preferred short-term intensive treatment option for this patient population.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis study received no funding support.\u003c/p\u003e\n\u003cp\u003eCompeting Interests\u003c/p\u003e\n\u003cp\u003eThe authors claim no conflict of interest in this study\u003c/p\u003e\n\u003cp\u003eAuthor Contributions\u003c/p\u003e\n\u003cp\u003eYaping Sun and Liwu Xu jointly designed the study and developed the protocol. Yaping Sun collected and analyzed the data and drafted the initial manuscript. Xiaolei Li assisted with statistical analysis and the preparation of figures and tables. Liwu Xu provided critical revisions to multiple versions of the manuscript. As the corresponding author, Liwu Xu assumes full responsibility for the integrity of the data, the accuracy of the analysis, and the work as a whole.\u003c/p\u003e\n\u003cp\u003eEthics Review and Institutional Affiliation\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Medical Ethics Committee of the First Hospital of Anhui University of Science and Technology (Ethics Approval No.2025-KY-Y026-001) and and is in accordance with the Declaration of Helsinki and registered with the China Clinical Trial Center.\u003c/p\u003e\n\u003cp\u003eConsent to participate\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eInternational Diabetes Federation(IDF), \u003cem\u003eIDF Diabetes Atlas\u003c/em\u003e, 10th edn. 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Health. \u003cb\u003e13\u003c/b\u003e, 1585279 (2025)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eT. Battelino, C.M. Alexander, S.A. Amiel et al., Continuous glucose monitoring and metrics for clinical trials: an international consensus statement. Lancet Diabetes Endocrinol. \u003cb\u003e11\u003c/b\u003e(1), 42\u0026ndash;57 (2023)\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"endocrine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"endo","sideBox":"Learn more about [Endocrine](https://www.springer.com/journal/12020)","snPcode":"12020","submissionUrl":"https://submission.nature.com/new-submission/12020/3","title":"Endocrine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Overweight/obesity, Type 2 diabetes, IDegLira, Insulin glargine, Short-term intensive glucose control","lastPublishedDoi":"10.21203/rs.3.rs-8921856/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8921856/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTo compare the efficacy of insulin degludec/liraglutide (IDegLira) versus insulin glargine, both combined with insulin aspart, for short-term intensive glycemic control in overweight or obese patients with type 2 diabetes mellitus (T2DM).\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e \u003cp\u003eSeverely hyperglycemic overweight/obese T2DM patients were randomly assigned to receive either IDegLira plus insulin aspart (observation group) or insulin glargine plus insulin aspart (control group). Continuous glucose monitoring systems (CGMS) were used to assess glycemic control, insulin requirements, pancreaticβ-cell function, and insulin resistance over a seven-day intensive therapy period.\u003c/p\u003e\u003ch2\u003eResult\u003c/h2\u003e \u003cp\u003eThe observation group exhibited a higher time in range (TIR) compared with the control group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007). Measures of glycemic variability, including time above range (TAR), mean of daily differences (MODD), mean glucose (MG), standard deviation (SD), and coefficient of variation (CV), were all significantly lower in the IDegLira group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01). After seven days of treatment, the reduction in C-peptide-based homeostasis model assessment of insulin resistance (HOMA-IR-CP) was greater in the IDegLira group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001), while the improvement in C-peptide-based homeostasis model assessment of β-cell function (HOMA islet-CPDM) was markedly greater(\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The IDegLira group also required a lower total daily insulin dose at the end of treatment, achieved glycemic targets more rapidly, and demonstrated a higher rate of excellent glycemic control (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eIDegLira combined with insulin aspart provides superior short-term intensive glycemic control compared with insulin glargine plus insulin aspart in overweight or obese patients with T2DM, with faster target achievement, improved glycemic stability, reduced insulin requirements, and greater improvements in insulin resistance and β-cell function.\u003c/p\u003e","manuscriptTitle":"Comparative Analysis of IDegLira versus Insulin Glargine in Short-Term Intensive Therapy for Overweight or Obese Patients with Type 2 Diabetes Mellitus","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-02 07:00:49","doi":"10.21203/rs.3.rs-8921856/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-05-01T13:03:25+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-30T18:22:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"116525725047124201352103608470422408324","date":"2026-04-19T17:30:00+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-29T20:10:35+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-21T14:30:01+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-21T14:29:17+00:00","index":"","fulltext":""},{"type":"submitted","content":"Endocrine","date":"2026-02-20T03:02:49+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"endocrine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"endo","sideBox":"Learn more about [Endocrine](https://www.springer.com/journal/12020)","snPcode":"12020","submissionUrl":"https://submission.nature.com/new-submission/12020/3","title":"Endocrine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"39e1a757-5a80-44a7-a022-4ea6b583e489","owner":[],"postedDate":"April 2nd, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-05-01T13:03:25+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-30T18:22:50+00:00","index":16,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-01T13:08:59+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-02 07:00:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8921856","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8921856","identity":"rs-8921856","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}